DOI: 10.1093/jnci/djr151 Advance Access publication on May 17, 2011.
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ARTICLE
Coffee Consumption and Prostate Cancer Risk and Progression in the Health Professionals Follow-up Study Kathryn M. Wilson, Julie L. Kasperzyk, Jennifer R. Rider, Stacey Kenfield, Rob M. van Dam, Meir J. Stampfer, Edward Giovannucci, Lorelei A. Mucci Manuscript received September 1, 2010; revised March 31, 2011; accepted April 1, 2011. Correspondence to: Kathryn M. Wilson, ScD, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02115 (e-mail:
[email protected]).
Background
Coffee contains many biologically active compounds, including caffeine and phenolic acids, that have potent antioxidant activity and can affect glucose metabolism and sex hormone levels. Because of these biological activities, coffee may be associated with a reduced risk of prostate cancer.
Methods
We conducted a prospective analysis of 47 911 men in the Health Professionals Follow-up Study who reported intake of regular and decaffeinated coffee in 1986 and every 4 years thereafter. From 1986 to 2006, 5035 patients with prostate cancer were identified, including 642 patients with lethal prostate cancers, defined as fatal or metastatic. We used Cox proportional hazards models to assess the association between coffee and prostate cancer, adjusting for potential confounding by smoking, obesity, and other variables. All P values were from two-sided tests.
Results
The average intake of coffee in 1986 was 1.9 cups per day. Men who consumed six or more cups per day had a lower adjusted relative risk for overall prostate cancer compared with nondrinkers (RR = 0.82, 95% confidence interval [CI] = 0.68 to 0.98, Ptrend = .10 ). The association was stronger for lethal prostate cancer (consumers of more than six cups of coffee per day: RR = 0.40, 95% CI = 0.22 to 0.75, Ptrend = .03). Coffee consumption was not associated with the risk of nonadvanced or low-grade cancers and was only weakly inversely associated with high-grade cancer. The inverse association with lethal cancer was similar for regular and decaffeinated coffee (each one cup per day increment: RR = 0.94, 95% CI = 0.88 to 1.01, P = .08 for regular coffee and RR = 0.91, 95% CI = 0.83 to 1.00, P = .05 for decaffeinated coffee). The age-adjusted incidence rates for men who had the highest (≥6 cups per day) and lowest (no coffee) coffee consumption were 425 and 519 total prostate cancers, respectively, per 100 000 person-years and 34 and 79 lethal prostate cancers, respectively, per 100 000 person-years.
Conclusions
We observed a strong inverse association between coffee consumption and risk of lethal prostate cancer. The association appears to be related to non-caffeine components of coffee.
J Natl Cancer Inst 2011;103:876–884
Coffee contains diverse biologically active compounds that include caffeine, minerals, and phytochemicals. Long-term coffee drinking has been associated with improved glucose metabolism and insulin secretion in observational and animal studies (1). Coffee is also a potent antioxidant (2–4) and may be associated with sex hormone levels (5–7). Coffee consumption has been consistently associated with a reduced risk of type 2 diabetes (8), and its effects on insulin, sex hormones, and antioxidants may also be relevant to prostate cancer. We hypothesized that coffee may be associated with lower risk of more advanced prostate cancers because the associations of insulin, antioxidants, and androgens with incidence of prostate cancer are stronger for advanced disease than for overall disease (9–15). 876 Articles
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Epidemiological studies of coffee consumption and prostate cancer have generally reported null results (16–30), although most lacked a wide range of coffee intakes and a large number of case subjects and none specifically examined advanced disease. The two studies of coffee consumption and prostate cancer mortality (31,32) found no statistically significant associations, but these were limited by a narrow range of intake, small number of cancer deaths, and inadequate adjustment for potential confounding. We investigated the relationship between coffee intake and risk of overall prostate cancer and of aggressive disease, defined as lethal, advanced, or high-grade cancer, in the Health Professionals Follow-up Study. Vol. 103, Issue 11 | June 8, 2011
Methods The Health Professionals Follow-up Study is a prospective cohort study of 51 529 male health professionals in the United States aged 40–75 years at baseline in 1986. The men are followed through biennial questionnaires to update information on lifestyle and health outcomes, and usual diet has been assessed every 4 years. Men who completed the baseline food frequency questionnaire (FFQ) in 1986 form the study population for this analysis (N = 49 911). We excluded men who had an implausible energy intake (4200 kcal/day) or who left more than 70 food items blank on the baseline FFQ. We also excluded men who reported a diagnosis of cancer (except nonmelanoma skin cancer) before baseline (N = 2000). This left a total of 47 911 men who were followed prospectively for cancer incidence until 2006 and for metastases and mortality outcomes until 2008. The Health Professionals Follow-up Study is approved by the Human Subjects Committee at the Harvard School of Public Health. Assessment of Coffee Intake Updated dietary data, including coffee consumption, was available from FFQs, which reported on intake of over 130 food items at baseline in 1986, and again in 1990, 1994, 1998, and 2002. Participants were asked how frequently they had consumed a specified portion size of each item over the previous year, with nine possible responses ranging from “never or less than once a month” to “six or more times per day.” The FFQ included questions concerning cups of decaffeinated and regular coffee intake. A validation study in this cohort found a high correlation (r = 0.93) between participants’ reports of coffee intake on the FFQ compared with two week-long diet records (33). Ascertainment and Classification of Subjects Who Developed Prostate Cancer Prostate cancer diagnoses were initially identified by self-reports from the participants or their next of kin on the biennial questionnaires and then confirmed by review of medical records and pathology reports. Deaths in the cohort were ascertained through reports from family members and searches of the National Death Index. Underlying cause of death was assigned by an endpoints committee based on all available data including medical history, medical records, registry information, and death certificates. Approximately 90% of prostate cancer patients were documented by medical records; the remaining 10% of men with prostate cancer, based on self-reports or death certificates, were included because the reporting of prostate cancer was highly accurate (>98%) among men with available medical records. We followed men with prostate cancer starting in 2000 with an additional prostate cancer–specific questionnaire separate from the regular Health Professionals Follow-up Study questionnaire every year to ascertain disease progression and diagnosis of metastases. We studied total prostate cancer incidence excluding stage T1a cancers, which are discovered incidentally during treatment for benign prostatic hypertrophy. Because of the considerable heterogeneity in the biological potential of prostate cancer, we also examined the data for men with advanced, lethal, or nonadvanced cancers separately to distinguish those patients in whom the canjnci.oxfordjournals.org
CONTEXT AND CAVEATS Prior knowledge Previous epidemiological studies have generally found no association between coffee consumption and risk of prostate cancer, but all such studies had limitations and none focused on advanced disease. Study design The association between coffee intake and risk of prostate cancer was prospectively analyzed among 47 911 men of the Health Professionals Follow-Up Study, who had repeatedly provided nutritional data since 1986. Cancer incidence was followed until 2006 and metastases and mortality until 2008. Relative risks were computed and adjusted for age, smoking, obesity, and other variables. Contribution Men who drank six or more cups of coffee per day had a slightly lower adjusted relative risk of prostate cancer and a substantially lower adjusted relative risk of lethal prostate cancer compared with nondrinkers. Both caffeinated and decaffeinated coffee consumption were associated with similarly reduced risks. Implications There may be biologically active compounds in coffee that protect against risk of lethal prostate cancer. Limitations The results depend on self-reported nutritional data and correction for multiple possible confounders. Coffee consumption was not found to be associated with risk of lower grade prostate cancers. From the Editors
cer was likely to progress clinically. Advanced cancers were those that had spread beyond the prostate, including to the seminal vesicle, lymph nodes, or bone. This category included men with stage T3b, T4, N1, or M1 prostate cancer at diagnosis, men who developed lymph node or distant metastases, and men who died of prostate cancer before the end of follow-up. Lethal cancers, a subset of advanced cancers, were those that caused death or metastasis to bone before the end of follow-up. Nonadvanced cancers were stage T1 or T2 and N0 and M0 at diagnosis and did not progress to lymph node or distant metastases or death during the follow-up period. (Some cancers that were diagnosed near the end of the follow-up period will be misclassified as nonadvanced because they had less time to progress before the end of follow-up). Cancers were also categorized as high grade (Gleason sum at diagnosis 8–10), grade 7, or low grade (Gleason sum 2–6) at diagnosis based on prostatectomy or biopsy pathology reports; Gleason grade was not available for all men with prostate cancer, particularly for those who were diagnosed earlier in the follow-up period. Statistical Analysis Each participant contributed person-time from the date on which he returned the baseline questionnaire in 1986 until prostate cancer diagnosis, death, or the end of the study period, January 31, 2006. Participants were followed for prostate cancer incidence until January 31, 2006, and for death and metastases until January JNCI
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31, 2008. Participants’ data were divided according to levels of total (regular and decaffeinated) coffee intake, and relative risks of prostate cancer were calculated as the incidence rate in a given category of intake divided by the rate in the lowest category, adjusted for age and calendar time. Because coffee intake may affect carcinogenesis over an extended period, we used the cumulative average intake of coffee to represent long-term dietary intake as our primary measure of exposure. That is, the coffee intake reported by particpants in 1986 was used to compute exposure for the 1986–1990 follow-up period, the average of the intakes reported in 1986 and 1990 was used for the 1990–1994 follow-up period, the average of intakes reported in 1986, 1990, and 1994 was used for the 1994–1998 follow-up period, and so on. In a secondary analysis, we used baseline (1986) coffee intake only. In addition, we used our repeated measures to analyze the effect of latency time (time from exposure to cancer diagnosis) by relating each measure of coffee intake to prostate cancer incidence during specific time periods: 0–4, 4–8, 8–12, and 12–16 years after exposure. Finally, to assess the potential for symptoms of subclinical advanced disease to affect coffee intake (reverse causation), we conducted a secondary analysis using cumulative average intake with a lag of 4 years to avoid using data on coffee consumption from FFQs completed immediately before diagnosis. We used Cox proportional hazards regression to adjust for potential confounding by prostate cancer risk factors previously identified in this cohort and in other studies. Scaled Schoenfeld residuals were used to test the proportional hazards assumption. Multivariable models were adjusted for race (White, African American, Asian American, other), height (quartiles), body mass index at age 21 (
